The complex influence of the combination of the BDNF (rs6265), VDR (rs2228570), and NMDA (rs4880213) genotypes on the development of cognitive disorders in patients with autoimmune thyroiditis andhypothyroidism

Abstract

Background. Numerous studies have demonstrated that thyroid conditions can affect cognitive function. Gene polymorphisms associated with pathology of the endocrine and nervous system have ethnic and population specificity, which determines the need to study them in a certain region. The purpose of the study was to investigate the combined impact of the BDNF (rs6265), VDR (rs2228570), and NMDA (rs4880213) gene polymorphisms on cognitive impairment in patients with autoimmune thyroiditis and hypothyroidism among the population of Western regions of Ukraine, and to predict the onset of cognitive disorders. Materials and methods. The study involved a total of 153 patients with autoimmune thyroiditis and hypothyroidism. Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA (rs4880213) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) was performed on CFX96™ Real-Time PCR Detection System (Bio-Rad Laboratories, Inc., USA). Polymerase chain reaction for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). We detect a decline in cognitive function using the Mini-Mental State Examination. Results. Carrying a combination of CC/AG/CC genotypes significantly reduces the risk of developing cognitive impairment (odds ratio (OR)=0.1410; 95% confidence interval (CI) 0.0181–1.0965; p=0.0416). At the same time, carrying a combination of CT/AG/CT genotypes increases the risk of cognitive impairment by more than 5 times (OR=5.1915; 95% CI 1.2471–21.6107; p=0.0214) and a combination of CT/AG/TT genotypes — by 10 times (OR=10.1224; 95% CI 1.1037–92.8401; p=0.0281). Carriers of the CT/AA/CT genotype combination have a 6.4-fold increased risk of cognitive impairment (OR=6.4062; 95% CI 1.2019–34.1471; p=0.0253). Conclusions. Among patients with autoimmune thyroiditis and hypothyroidism, carriers of the CC/AG/CC genotype combination of the BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) genes have a reduced risk of developing cognitive disorders, while carriers of the CT/AG/CT, CT/AG/TT and CT/AA/CT have an increased risk of cognitive impairment.